This Special Mental Health-Clinical Research Center renewal application requests funding for infra-structure which supports a program of research on the classification and course of the schizophrenias. Schizophrenia is a syndrome heterogenous in its manifestation across patients. In the application of clinical theory and construct, investigators at this SMH- CRC has demonstrated reduction of heterogeneity relevant to brain structure and function as assessed with MRI, PET, post-mortem tissue, neuropsychological and cognitive performance, neurological signals, childhood development, oculomotor physiology, evoked potential, and etiologically relevant data on season of birth, pathology in biological relatives, and seropositivity for borna disease virus. The same approach to heterogeneity reduction results distinctive pharmacologic response profiles in course studies involving clinical trials methodology. Base don the importance of ethical issues on which schizophrenia research is now receiving intense scrutiny, this SMH-CRC has developed a new program of work on informed consent/ethics. Project support for the SMH-CRC investigators is obtained through competitive federal and foundation grants. Infra-structure support is provided through the following modules: Scientific Support, Assessment, Data Management, Clinical Biology and Subject Recruitment. A separately funded Training module is integral to the Center. The basic neuroscience faculty, also funded from other sources, greatly enriches the activities of the SMH-CRC.